Tag Archive for: remission

What Are the Treatment Goals for Follicular Lymphoma?

What Are the Treatment Goals for Follicular Lymphoma? from Patient Empowerment Network on Vimeo.

Dr. Tycel Phillips reviews the main treatment goals for follicular lymphoma. Dr. Phillips provides insight on treatment decisions based on the patient’s staging and symptoms. 

Dr. Tycel Jovelle Phillips is a Medical Oncologist in the Hematology Clinic at The University of Michigan Rogel Cancer Center. Learn more about Dr. Phillips, here.

See More from The Pro-Active Follicular Lymphoma Patient Toolkit

Related Programs:

 
Follicular Lymphoma: What Treatment Options Are Available?

Follicular Lymphoma: What Treatment Options Are Available?

What Factors Are Considered When Choosing a Follicular Lymphoma Treatment?

What Is the Patient’s Role in Follicular Lymphoma Decisions?

What Is the Patient’s Role in Follicular Lymphoma Decisions?


Transcript:

Katherine:                  

How about we begin with treatment goals? What does this mean exactly and what are the goals of treatment for follicular lymphoma?

Dr. Phillips:                 

So, for the vast majority of patients, follicular lymphoma unfortunately to date is not curable. So, for those patients the goal of treatment when we initiate treatment is to alleviate any symptoms that may be caused by the lymphoma.

So, the patient has fevers, they have night sweats, or there’s some sort of organ damage from the cancer, our goal of treatment is to reverse that and put the cancer into what we call a remission. Remission basically means that from the test that we have currently, we cannot find any evidence of the cancer. That does not mean that you’re cured from the cancer. Patients with earlier stages – so, if you have a patient with stage one or a localized stage two, we approach that with a little bit of a different treatment mindset.

So, if we can catch it early enough, which is very hard given because of the cancer. So, these are really incidentally found, and in some cases, by luck. We can potentially cure follicular lymphoma in these patients. But that’s more of a curative intent with radiation and not systemic therapy. With the advent of PET scans, which have made it a little bit easier to find all the hidden areas of where the follicular lymphoma may hide out, concurrently with a bone marrow biopsy, if a patient is truly stage one, we will initiate therapy with a curative intent.

Whereas, again, with the other patients, our goal is just to control the symptoms and put you into remission.

What Are the Stages of Follicular Lymphoma?

What Are the Stages of Follicular Lymphoma? from Patient Empowerment Network on Vimeo.

How does follicular lymphoma progress? Expert Dr. Tycel Phillips discusses the disease’s stages and the impact on treatment options.

Dr. Tycel Jovelle Phillips is a Medical Oncologist in the Hematology Clinic at The University of Michigan Rogel Cancer Center. Learn more about Dr. Phillips, here.

See More from The Pro-Active Follicular Lymphoma Patient Toolkit

Related Programs:

What Is Follicular Lymphoma?

What Is Follicular Lymphoma?

What Are the Treatment Goals for Follicular Lymphoma?

What Are the Treatment Goals for Follicular Lymphoma?

What Factors Are Considered When Choosing a Follicular Lymphoma Treatment?


Transcript:

Katherine:                  

You’ve touched upon this briefly, but what are the stages of follicular lymphoma? How does it progress?

Dr. Phillips:                 

So, when we talk about follicular lymphoma, so, in stages there are four stages. Stage one, which means it’s localized in one general area. Or potentially into one organ. Stage two means that it is on one side of the diaphragm. So, we use your diaphragm as sort of a dividing point. Sort of like a Mason-Dixon line of the body. So, if it’s all on one side, it’s a stage two. If you have disease both above and below the diaphragm, you’d be considered to be stage three. Stage four indicates that you either have an organ involved in a nonadjacent lymph node.

So, let’s just say there’s a spot in your liver and you have a lymph node in your neck, or if your bone marrow is involved. For the most part, most patients with follicular lymphoma, because again, when develops, it doesn’t really develop with symptoms and typically is in there for quite a bit of time. Most patients will have what we consider to be advanced stage of this disease, meaning it’s stage three or four. Because the cancer has quite a bit of time to grow and move around before we find it.

It also comes in a set of grades. So, stage and grades are different. Stage is location, grade is what the pathologist sort of looks at when he looks under a microscope – how angry or big the cells look. So, we typically divide it into grades one and two; it’s very hard to separate one and two, so it’s generally grouped together. Which means there are mostly small round cells and very few big cells. And then we have grade 3A and grade 3B. And grade 3A means that when they look at it under the microscope, they see a fair number of larger cells which means that’s probably a bit more aggressive than the grade one to two.

And grade 3B is sort of separated into a category of its own. And we tend to treat grade 3B as a more aggressive lymphoma. we treat that very closely, like we treat the diffuse large B-cell lymphomas. So, grade 3B is in a category of its own, and then grades one to two and grade three are sort of clumped together.

What Is Follicular Lymphoma?

What Is Follicular Lymphoma? from Patient Empowerment Network on Vimeo.

Dr. Tycel Phillips gives his expert definition of follicular lymphoma and explains why this disease is often found incidentally. 

Dr. Tycel Jovelle Phillips is a Medical Oncologist in the Hematology Clinic at The University of Michigan Rogel Cancer Center. Learn more about Dr. Phillips, here.

See More from The Pro-Active Follicular Lymphoma Patient Toolkit

Related Programs:

What are the stages of Follicular Lymphoma?

What Are the Stages of Follicular Lymphoma?

What Are the Treatment Goals for Follicular Lymphoma?

What Are the Treatment Goals for Follicular Lymphoma?

What Factors Are Considered When Choosing a Follicular Lymphoma Treatment?


Transcript:

Katherine:                  

What exactly is follicular lymphoma?

Dr. Phillips:                 

So, follicular lymphoma is a malignant growth or tumor in some situations, depending on how you want to describe it, of lymphocytes. Lymphocytes are normal cells that we have in our body and are a very important part of our immune system. For a very generic sort of description, lymphocytes come in what we call B and T-cells. B-cells, as I mentioned, are the cells that help make antibodies and it’s how we fight viruses and other diseases. These antibodies help our immune system recognize and hopefully clear these pathogens quicker.

And then we also have T-cells, which I like to refer to as like jailers, who will survey and sort of try to eliminate any abnormal cells. Lymphoma can come in a B-cell lymphoma or a T-cell lymphoma. For western Europe and the U.S., B-cell lymphomas account for the vast majority of cases of lymphoma; about 85%. When we look at B-cell lymphomas, we have Hodgkin’s Lymphomas, which are a separate category, and non-Hodgkin’s lymphomas.

And follicular lymphoma is the most common indolent, or what we consider slow growing, of non-Hodgkin’s lymphomas. So, when we talk about indolent as slow growing, these are lymphomas that are more than likely to be found incidentally by CAT scans. Or if you’re going for some other procedure, they’ll notice that you have enlarged lymph nodes and a biopsy will lead to a diagnosis of follicular lymphoma. In most cases, the cancer has probably been there for several years, at least months, before it’s been found. And in most cases, most patients have been living happily unbeknownst to them together with this cancer.

And so, follicular lymphoma being in that way is something that, again, we consider to be slow growing because, again, the more aggressive lymphomas tend to come with symptoms. So, these can come on more insidiously and are typically found incidentally.

Is the COVID Vaccine Safe and Effective for Follicular Lymphoma Patients?

Is the COVID Vaccine Safe and Effective for Follicular Lymphoma Patients? from Patient Empowerment Network on Vimeo.

Dr. Tycel Phillips discusses the efficacy and safety of the COVID vaccine for follicular lymphoma patients. Dr. Phillips reviews the effects it may have on patients and provides his expert advice.

Dr. Tycel Jovelle Phillips is a Medical Oncologist in the Hematology Clinic at The University of Michigan Rogel Cancer Center. Learn more about Dr. Phillips, here.

See More from The Pro-Active Follicular Lymphoma Patient Toolkit

Related Programs:

What Are the Treatment Goals for Follicular Lymphoma?

What Are the Treatment Goals for Follicular Lymphoma?

What Factors Are Considered When Choosing a Follicular Lymphoma Treatment?

What Is the Patient’s Role in Follicular Lymphoma Decisions?

What Is the Patient’s Role in Follicular Lymphoma Decisions?


Transcript:

Katherine:                  

Is the COVID vaccine safe and effective for follicular lymphoma patients?

Dr. Phillips:                 

So, the vaccine is safe. The effectiveness of the vaccine does in some part depend on whether the patients are untreated or they’re currently on treatment. Some of the treatments that we use to combat follicular lymphoma and other lymphomas unfortunately targets one of the key cells in the response to the vaccine. So, as follicular lymphoma is a cancer of the malignant B-cell, one of our treatments are directed, you know, obviously killing off malignant B-cells. And unfortunately, we do take some innocent bystanders. So, your normal B-cells will be impacted, which does sometimes impact your abilities to make antibodies.

But we do know from research that the vaccines will also trigger a T-cell response, which most of our treatments will not impact. So, well, we do recommend for our patients to be vaccinated. Because, again, it is safe. And, again, it is effective even if it’s not as effective as it would be if you weren’t on treatment.

Katherine:                  

Mm-hmm. Better to be safe than sorry.

Dr. Phillips:                 

Yes.

Follicular Lymphoma Treatment Decisions: What’s Right for You?

Follicular Lymphoma Treatment Decisions: What’s Right for You? from Patient Empowerment Network on Vimeo.

When considering therapy for follicular lymphoma, what determines the best treatment for YOU? Dr. Tycel Phillips reviews key factors for making treatment decisions, tips for partnering with your healthcare team, and shares an update on emerging treatment and research.

Dr. Tycel Jovelle Phillips is a Medical Oncologist in the Hematology Clinic at The University of Michigan Rogel Cancer Center.

See More from The Pro-Active Follicular Lymphoma Patient Toolkit

Download Guide

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Transcript:

Katherine:             

Hello and welcome. I’m Katherine Banwell, your host for today’s webinar. In this program, we’re going to learn more about follicular lymphoma. What it is, how it’s treated, and we’ll share tools to help you work with your healthcare team to access the best care. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to program materials.

If you haven’t already, click that link to access information to follow along during the webinar. At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars. And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Joining me today is Dr. Tycel Phillips. Welcome, Dr. Phillips. Would you please introduce yourself?

Dr. Phillips:                 

Hi, I’m Dr. Tycel Phillips. I’m an associate professor at the University of Michigan. I look forward to talking today.

Katherine:                  

Good. Thank you so much for taking the time out of your schedule. Before we learn about follicular lymphoma, let’s start with a question we’ve received that’s on the minds of many patients. Is the COVID vaccine safe and effective for follicular lymphoma patients?

Dr. Phillips:                 

So, the vaccine is safe. The effectiveness of the vaccine does in some part depend on whether the patients are untreated or they’re currently on treatment. Some of the treatments that we use to combat follicular lymphoma and other lymphomas unfortunately targets one of the key cells in the response to the vaccine. So, as follicular lymphoma is a cancer of the malignant B-cell, one of our treatments are directed, you know, obviously killing off malignant B-cells. And unfortunately, we do take some innocent bystanders. So, your normal B-cells will be impacted, which does sometimes impact your abilities to make antibodies.

But we do know from research that the vaccines will also trigger a T-cell response, which most of our treatments will not impact. So, well, we do recommend for our patients to be vaccinated. Because, again, it is safe. And, again, it is effective even if it’s not as effective as it would be if you weren’t on treatment.

Katherine:                  

Mm-hmm. Better to be safe than sorry.

Dr. Phillips:                 

Yes.

Katherine:                  

Let’s start at the very beginning. What exactly is follicular lymphoma?

Dr. Phillips:                 

So, follicular lymphoma is a malignant growth or tumor in some situations, depending on how you want to describe it, of lymphocytes. Lymphocytes are normal cells that we have in our body and are a very important part of our immune system. For a very generic sort of description, lymphocytes come in what we call B and T cells. B cells, as I mentioned, are the cells that help make antibodies and it’s how we fight viruses and other diseases. These antibodies help our immune system recognize and hopefully clear these pathogens quicker.

And then we also have T cells, which I like to refer to as like jailers, who will survey and sort of try to eliminate any abnormal cells. Lymphoma can come in a B-cell lymphoma or a T-cell lymphoma. For western Europe and the U.S., B-cell lymphomas account for the vast majority of cases of lymphoma; about 85 percent. When we look at B-cell lymphomas, we have Hodgkin’s Lymphomas, which are a separate category, and non-Hodgkin’s lymphomas.

And follicular lymphoma is the most common indolent, or what we consider slow growing, of non-Hodgkin’s lymphomas. So, when we talk about indolent as slow growing, these are lymphomas that are more than likely to be found incidentally by CAT scans. Or if you’re going for some other procedure, they’ll notice that you have enlarged lymph nodes and a biopsy will lead to a diagnosis of follicular lymphoma. In most cases, the cancer has probably been there for several years, at least months, before it’s been found. And in most cases, most patients have been living happily unbeknownst to them together with this cancer.

And so, follicular lymphoma being in that way is something that, again, we consider to be slow growing because, again, the more aggressive lymphomas tend to come with symptoms. So, these can come on more insidiously and are typically found incidentally.

Katherine:                  

You’ve touched upon this briefly, but what are the stages of follicular lymphoma? How does it progress?

Dr. Phillips:                 

So, when we talk about follicular lymphoma, so, in stages there are four stages. Stage I, which means it’s localized in one general area. Or potentially into one organ. Stage II means that it is on one side of the diaphragm. So, we use your diaphragm as sort of a dividing point. Sort of like a Mason-Dixon line of the body. So, if it’s all on one side, it’s a stage II. If you have disease both above and below the diaphragm, you’d be considered to be stage III. Stage IV indicates that you either have an organ involved in a nonadjacent lymph node.

So, let’s just say there’s a spot in your liver and you have a lymph node in your neck, or if your bone marrow is involved. For the most part, most patients with follicular lymphoma, because again, when develops, it doesn’t really develop with symptoms and typically is in there for quite a bit of time. Most patients will have what we consider to be advanced stage of this disease, meaning it’s stage III or IV. Because the cancer has quite a bit of time to grow and move around before we find it.

It also comes in a set of grades. So, stage and grades are different. Stage is location, grade is what the pathologist sort of looks at when he looks under a microscope – how angry or big the cells look. So, we typically divide it into grades 1 and 2; it’s very hard to separate one and two, so it’s generally grouped together. Which means there are mostly small round cells and very few big cells. And then we have grade 3A and grade 3B. And grade 3A means that when they look at it under the microscope, they see a fair number of larger cells which means that’s probably a bit more aggressive than the grade 1 to 2.

And grade 3B is sort of separated into a category of its own. And we tend to treat grade 3B as a more aggressive lymphoma. we treat that very closely, like we treat the diffuse large B-cell lymphomas. So, grade 3B is in a category of its own, and then grades 1 to 2 and grade 3 are sort of clumped together.

Katherine:                  

Okay. That’s very helpful, thank you. Now that we know more about follicular lymphoma and how it’s staged, let’s move on to treatment approaches. Many factors come into play, right, when making a treatment decision. Including a patient’s age and overall health. So, let’s walk through these considerations. How about we begin with treatment goals? What does this mean exactly and what are the goals of treatment for follicular lymphoma?

Dr. Phillips:                 

So, for the vast majority of patients, follicular lymphoma unfortunately to date is not curable. So, for those patients the goal of treatment when we initiate treatment is to alleviate any symptoms that may be caused by the lymphoma.

So, the patient has fevers, they have night sweats, or there’s some sort of organ damage from the cancer, our goal of treatment is to reverse that and put the cancer into what we call a remission. Remission basically means that from the test that we have currently, we cannot find any evidence of the cancer. That does not mean that you’re cured from the cancer. Patients with earlier stages – so, if you have a patient with stage I or a localized stage II, we approach that with a little bit of a different treatment mindset.

So, if we can catch it early enough, which is very hard given because of the cancer. So, these are really incidentally found, and in some cases, by luck. We can potentially cure follicular lymphoma in these patients. But that’s more of a curative intent with radiation and not systemic therapy. With the advent of PET scans, which have made it a little bit easier to find all the hidden areas of where the follicular lymphoma may hide out, concurrently with a bone marrow biopsy, if a patient is truly stage I, we will initiate therapy with a curative intent.

Whereas, again, with the other patients, our goal is just to control the symptoms and put you into remission.

Katherine:                  

What is considered when choosing a treatment? Are there test results that can impact the options?

Dr. Phillips:                 

So, there are. So, for the most part we’ll take a couple of things into consideration. So, there is no standard of care for follicular lymphomas. So, there are a couple different options that can be utilized in the upfront setting for the untreated patient. So, comorbidities play a part in what sort of treatment we choose. Patient’s age and fitness will play a part. If there’s any heart disease, that will play a part in the situation as well. And also, as I said, stage will play a part in sort of what our treatment goals are.

So, if our treatment goal for a really unfit patient who we don’t think can tolerate chemotherapy, it’s just symptom control. And they don’t have a lot of disease, we can sometimes treat them with just a monoclonal antibody we call rituximab (Rituxan) as a single agent.

If the patient has a lot of disease, and they are a fit patient, we will tend to combine rituximab with several different chemotherapy regimens. Because rituximab plus chemotherapy works better than chemotherapy and also rituximab alone, especially depending on the amount of the disease that we’re trying to treat. And again, as I mentioned before, if it’s a localized patient there is known to be radiation plus or minus rituximab in that situation.

But because of some of the side effects of the drugs we use, and obviously now we’re in a pandemic, a lot of those will take sort of some of the consideration of what we use. Some of the drugs that we use are either more sort of immunosuppressants than others, and obviously being in a pandemic, we have to take that into consideration because we’re not treating to cure. Some of the drugs can cause heart damage, some of the drugs can damage nerves, some of the drugs include steroids, which might be prohibited with some patients. So, all that sometimes has to be taken into consideration when we choose our regimen.

Katherine:                  

Yeah. It sounds like there are a lot of factors coming into play here.

Dr. Phillips:                 

Yeah, I mean normally, without a pandemic there’s a lot of factors, and the pandemic just makes things a little bit harder. Just because, again, our patients are already at risk based with some of the treatments we choose.

Katherine:                  

Yeah. Yeah. It’s pretty challenging right now. Does treatment typically start right away?

Dr. Phillips:                 

So, that really depends on a stage and also whether we meet certain sort of criteria to treat. So, we don’t have to treat right away. So, if a patient has a disease, and the disease is not in an area where we think it’s curative, for the most part we can enter into what we call a watch and wait. Meaning we will observe a patient very closely and defer treatment until the patient develops symptoms or other indications that warrant treatment.

We do know that there is no impact on longevity by sort of partaking in this approach. So, you won’t live any longer or you won’t live any shorter if we watch and wait versus initiating therapy right away. It just saves you from having some of the toxicities from treatment without any real major benefits.

So, remember the goal for most patients with follicular lymphoma is to alleviate symptoms or problems. If you don’t have a symptom or a problem, me giving you treatment is not going to make you feel any better. Actually, it would probably make you feel a little bit worse. To get you back to where you were when you started.                    

Katherine:                  

Yeah, right. What do you feel is the patient’s role in treatment decisions?

Dr. Phillips:                 

So, I know historically a lot of times, you come into an office, and we tell you what you’re going to get and what you’re not going to get. Patients nowadays are I would say a lot more savvy as far as what drugs are out there. And there are a lot more sort of conversational groups on social media between patients who’ve had treatment before and newly diagnosed patients. So, patients come in with a lot more information than they had historically had before. So, in that point, I think it’s more of an open dialogue about what options we have, what options are best for you, and what our treatment goals are at that point.

But all it means, given that we don’t yet have a standard of care, it leaves it open for discussion about sort of which route we choose to try to get your cancer under control.

Katherine:                  

Mm-hmm. Dr. Phillips, if a patient isn’t feeling confident with their treatment plan or their care, do you think they should consider a second opinion or a consult with a specialist?

Dr. Phillips:                 

I think a second opinion is probably best for all patients. It’s always probably good to get a different opinion about how the disease will be treated. So, I do encourage all my patients, even here, to get a second opinion. Some take me up on it, others won’t. But the option is always there to get a second opinion, just to see if anybody would do things any differently.

And I would say for the most part, most people would tend to treat the same way. Very seldom do we have differences in what our treatment recommendations would be. I think the biggest difference in some situations, it’s really about some patients are very uncomfortable being watched with an active cancer. And so, in that situation, that’s probably the biggest discrepancy we have nowadays.

Because of the anxiety of the watch and wait approach. Some patients would like treatment right away, irrespective of whether they need it or not. So, you’ll sometimes get discrepancies with our patients about that.

Katherine:                  

Mm-hmm. What would you say to a patient who may be nervous about offending their current doctor by getting a second opinion?

Dr. Phillips:                 

You shouldn’t be. If your doctor is offended because you’re getting a second opinion, that’s probably not the doctor for you. Yeah, I think that at this point, any physician that’s confident in their decision they’re giving you should not be offended if you go seek reassurance from somebody else.

Katherine:                  

Yeah, good advice. Thank you. Now that we’ve discussed factors that can impact treatment decisions, would you walk us through the currently available follicular lymphoma treatment approaches? And who they might be right for?

Dr. Phillips:                 

Sure. So, we’ll start with the newly diagnosed or untreated patient. So, again, if you’re newly diagnosed or untreated, your options are the monoclonal antibody, Rituximab. Again, that’s a CD20 monoclonal antibody.

That is typically given once weekly for four weeks and can be repeated, if need be, after a break. And that’s usually reserved for patients who have minimal symptoms, low burden disease. Because, again, data has shown that the bulkier the disease, you’re likely not to have a very durable or deep response with just simulating Rituximab. Additional options include Rituximab plus chemotherapy.

So, we have regimens such as CDP, which is Cytoxan, vincristine, and prednisone. Cytoxan and vincristine being a steroid, prednisone being — sorry, Cytoxan and vincristine being a chemotherapy agent, and prednisone being a steroid. We have our bendamustine, bendamustine being a chemotherapy agent. There’s R-CHOP, which is Cytoxan, vincristine, Adriamycin, and prednisone. And sometimes that is reserved, because unlike the other two, R-CHOP can only be given once because of the accumulation of the anthracycline.

You can only have so much of that in a lifetime before you run a risk of cardiac toxicity.

Katherine:                  

Oh.

Dr. Phillips:                 

And also, R-CHOP as of right now is a standard of care for diffuse large B-cell lymphoma. Which every patient with follicular lymphoma has a chance of transforming into diffuse large B-cell lymphoma at some point. So, we tend to try to reserve R-CHOP if we can. Additionally, more recently, there was a study called Relevance, which evaluated RPMO versus an agent called lenalidomide plus Rituximab, what we call R squared.

So, it was designed as a superiority study, but what came out of it is R squared is probably equivalent, not better, than R chemo. So that is also an option up front. With lenalidomide it’s a little bit different than the other agents, which all give it intravenously, meaning through the vein. But lenalidomide is an oral medication, that you would take 21 days on, and seven days off. And that’s given in conjunction with the Rituximab. And you typically would take that for 12 cycles, or about a year of treatment.

Whereas the chemotherapy regimens that I mentioned before, are typically given for six cycles. Meaning you’ll be taking it for a duration of 18 weeks or 24 weeks. So around four and half to six months for the chemotherapy. Thereafter, it’s a bit controversial, but some patients can then transition to what we call Rituximab maintenance.

Where you would get Rituximab every other month for a period of two to three years. Typically, two years, as a way to delay the return of the cancer. So, R maintenance we know of improves your progression of survival, so the time until the cancer comes back. And there is no survival benefit with maintenance at this point. So, it is in some ways a bit controversial. Especially now, given the pandemic.

Katherine:                  

What about stem cell transplant? Is that an option?

Dr. Phillips:                 

So, for up front, that’s usually not something that we typically do. So, for stem cell transplantation, there are two types of stem cell transplantation. There’s one called an Autologous Stem Cell Transplantation, which is basically really a stem cell rescue.

You get a high dose of chemotherapy after stem cells are collected from you and those stem cells are given back to rescue your body from the chemo. That is typically reserved for what we call high risk patients. So, we give you an initial up front chemotherapy regimen. And if your cancer comes back within less than 24 months of completion of that therapy, you fall into what we call a POD24 category. Which means Progression of Disease within 24 months.

We do know those patients are at higher risk, than patients who stay in remission for at least 24 months or longer. So, if we look at overall survival for those POD24 patients, about half of those patients will succumb to their disease within a five-year period. Which is much different for what we see with the standard for follicular lymphoma patients. So, and that POD24 category it does appear that Autologous Stem Cell Transplantation is beneficial in that patient population. As well as an Allogenic Stem Cell Transplant. So, an allogenic transplant is when you get immune cells from another donor.

So, “allo” meaning from a different person. So, in that sense, you get sort of temporized, and they would give you donor lymphocytes. And those lymphocytes themselves would try to fight off your cancer. So, an Auto transplant is mainly just chemo; an Allo transplant, the donor cells help fight off the cancer.

Katherine:                  

Right.

Dr. Phillips:                 

There are complications to both, which is why they’re not typically given up front. The Allo transplant probably has more risk of complications as well. Those cells can also recognize your body as being foreign and try to fight them off because they don’t originate from you. And there’s also just a risk of other death from that procedure. So, all those have to be taken with a bit of caution. And for the Allo transplant, it’s generally only recommended if you have that, a sibling donor. Because there’s much less risk of complications than versus you get an unrelated donor.

Katherine:                  

Right. Right, that makes sense. If someone receives treatment and then goes into remission, how are they monitored?

Dr. Phillips:                 

So, there’s a couple of different ways you can go about it.

Historically, what we would do is we would actually sometimes get CAT scans. But we’ve sort of pulled back from that in recent years. So, as of right now, the recommendation is really just clinical observation, meaning what I call well baby visits. Meaning I will see you in clinic at least every three months for the first year after completion of therapy. We do a system assessment, we’ll do a physical exam, we’ll do labs. Unless there is really something that at the completion of therapy that I’m concerned about, we won’t typically do any imaging.

We reserve imaging until there is a concern at some point, whether you have symptoms, there’s a lab issue, or there’s some other finding that comes up that means that we have to repeat pictures. So those visits I’ll do typically every three months for the first year, spaced out that every four months for the second year, post treatment. And then every six months up until about year four. And then it’ll become a yearly visit thereafter, as long as you continue to remain well without symptoms and nothing on an exam that’s concerning.

Katherine:                  

Yeah. We received this question from an audience member prior to the program. Angela asks, “What if I relapse after treatment? What are my options then?”

Dr. Phillips:                 

So, a lot of that, again, depends on the timing. If you relapse early, obviously whatever we gave you in the frontline we would not repeat. And again, if it’s within the 24-month period, again, that takes you on the road of POD24. Wherein patients who are fit enough, it would take you to a route where you would actually probably get a transplant. It’s consolidation to extend our true progression sabbatical.

If you relapse after 24 months, that would really depend on what you received in the frontline because some of these agents can be repeated. If we don’t repeat what you’ve had in a frontline setting – so again, if you’ve got R chemo, then a second line setting, normally what we would do now, based on published data from the augment study, is we would typically treat these patients with Rituximab and lenalidomide, which is that oral medication.

That’s typically if you did receive lenalidomide in the frontline setting and you would not want to repeat that, then we would typically give you R chemo in a second line setting. Again, in most of those situations, it would be RCP or Bendamustine and Rituximab.

Katherine:                  

Okay. Are there emerging approaches for treating follicular lymphoma that patients should know about?

Dr. Phillips:                 

There are. So, there are some more exciting data that’s coming out, specifically looking at CAR-T, which is chimeric antigen receptor therapy. So, these are augmented T cells that they collect from the patient, they help recognize – they help to modify those cancer cells to recognize the tumor more appropriately. And they target those tumor cells through a receptor called CD19 that’s present on the tumor.

So, that therapy has shown a significant overall response rate in follicular lymphoma. Even in very heavily pretreated patients. Right now, we’re still waiting on a longer follow up as far as the duration of the response, but as of right now it is a very encouraging therapy.

The downside to that therapy is that you can only receive it at select centers because they have to be a therapeutic approved center. So, you can’t just go sometimes to your regular oncologist’s in say, Skoboken or wherever, and get this treatment. So that’s one downside to that and also, it’s a very expensive treatment and you need insurance approval to cover that. Some of the side effects from that treatment we have gotten better at controlling, such as cytokine release syndrome, which can cause fever, low blood pressures, difficulty breathing.

That typically happens within a set period of time after the infusion of the [inaudible] and modified T cells. And then there’s also what we call neurotoxicity, meaning you can have some neurological complications. Which, again, we’ve become better at managing. There are a couple CAR-T products on the market right now; all of them seem very comparable and also effective in follicular lymphoma. There’s also treatments called bispecific antibodies, these are like causally off the shelf products, except they use an antibody.

And in this antibody it has sort of two receptors. So, earlier we talked about Rituximab, which is a CD20 antibody. The bispecifics have a CD20 antibody and a CD3 antibody set. So, they bind to the tumor and also bind to your T cells. And with the binding to the T-cells, they call it T-cell activation and expansion. And it will utilize your own T cells to fight off the cancer. So, because these bispecifics are given as an off the shelf product, they can likely be able to be given in more accessible areas.

So, you won’t have to select centers to be given. There are still some complications with those, such as CRS and neurotoxicity, but early reports indicate that they’re much less severe and less frequency than what we see with CAR-T. But as of right now, neither the duration of responses of these treatments are still to be determined. So, again, these are two exciting sort of avenues that are moving forward for patients with follicular lymphoma that will be further developed and sort of be expanded on in the coming years.

Katherine:                  

What about clinical trials? How do they fit in?

Dr. Phillips:                 

So, for patients with relapsed refractory disease and even some patients with untreated disease, clinical trials are sometimes your best avenue for getting some of these new and promising therapeutics before they get approval. I know sometimes patients are very cautious about clinical trials because they don’t want to be guinea pigs. But I would say all treatments that we offer you have started in clinical trials. And this is the only way to really advance the field. So, if your treating physician has a clinical trial for you, I would strongly recommend patients consider that.

Because, again, they are typically offering you something that they can’t offer you as a standard care, insurance approved treatment. And for the most part, they’re either adding drugs to what we do as far as standard of care treatment approach or offer you something that is very promising in the relapsed refractory setting or upfront setting. That compares very favorably to what we would give you as a standard of care option. That allows you to get this option sooner and earlier when you’re in better shape and less sort of beat up from the other treatments that we would give you.

Katherine:                  

I’d like to just go back for a second and ask you about inhibitor treatments.

Dr. Phillips:                 

Sure. So, as of right now, CAR-T with the chimeric antigen receptor therapy treatment is only approved for patients with relapsed refractory disease. The bispecific antibody therapies are only available in clinical trial. There are some other sort of cyclin inhibitors that haven’t gotten approval. So, we have the PO3 kind of Delta inhibitors, which inhibit the PO3 kind of pathway in a patient with follicular lymphoma.

There were four approved agents in this class of drugs. We had umbralisib, duvelisib, copanlisib, and idelalisib. More recently, two of those, idelalisib and duvelisib, have removed their indications for follicular lymphoma.

So, as of right now we have copanlisib which is an IDP kind of three dose inhibitor and umbralisib, which is an oral agent for the PO3 dose kind of inhibitor. So, both of those agents are typically usually targeted in the third line and beyond. So, patients who fail at least two lines of therapy. We also have tazemetostat, which is an EZH2 inhibitor, that was most recently improved. So, EZH2 mutations occur in about 20% of patients for follicular lymphoma.

But tazemetostat was actually approved for those with and without the mutation as it did show some efficacy in both. It appeared that the overall response rate was a bit higher than those who had an EZH2 mutation, with the duration of the response appears to be equivalent. But I do think for most parts in that situation, for those who lack the mutation the drug is typically used for patients who are unfit for other therapies. Whereas those who have the mutation, it typically probably will be used a bit earlier.

Katherine:                  

Okay. Excellent. Let’s take a moment to talk about patient self-advocacy. Patients can sometimes feel like they’re bothering their healthcare team with their questions and their comments. Why is it important for patients to speak up when it comes to symptoms and side effects?

Dr. Phillips:                 

Well, for the side effect part it’s important because your physician can’t potentially prevent the worst thing or further development of side effects. Nobody can. And also, they can’t prevent you from going to the hospital if you don’t let them know you have this certain side effects.

So, it’s very important to communicate side effects, because for the most part there are logical next steps that we can implement to either eliminate the side effects or hopefully prevent them from future treatment regimens. And also, other concerns that you may have. I mean, you only get one life. And this is your body. Then for the best part, it’s best to communicate any concerns that you may have in regard to treatment, or any questions you may have so that you are well aware.

You can’t really fight this appropriately without sort of being well aware of what you’re dealing with, what we’re using to take care of the cancer, and what potential side effects may come up. Again, so we can, again, have you have the best experience possible to try to get your cancer under control. I try to explain to my patients, “I don’t want you to wait until the next visit if you have issues.” I mean, we need to sort of manage these in real time. Even things we don’t take care of right then and there, again, it gives us a heads up and a head start to try to take care of these problems the next time you come to the clinic.

Katherine:                  

Dr. Phillips, to close, what would you like to leave the audience with? Are you hopeful?

Dr. Phillips:                 

So, I think follicular lymphoma, and lymphoma in general, we are having a better understanding of the biology of the cancer, certain things that are important to the cancer, and certain avenues that we can treat the cancer and avoid some toxicities that have sort of plagued us before. So, I think moving forward there is a ton of research going into improving outcomes for patients with lymphoma, and follicular lymphoma, in general. There are a ton of other treatment options that are coming down the pipe way.

So, I think patients with follicular lymphoma should be very hopeful and encouraged that we will just continue to improve the quality of life and also the duration that they can live with this cancer. I mean, as of right now, until we can cure this cancer, our real goal is to continue to buy you more time. And time buys you more treatments. And most of the treatments that we are developing and are coming, again, down the pipeline are less toxic than some of the things we had 5, 10, definitely 15, 20 years ago.

So, your experience and your quality of life will be improved, and these treatments will also give you more longevity than you could have ever expected. So, patients with lymphoma are living a lot longer and that’s not an important thing to remember. Not hopeful, not – sorry, it’s not hopeless, even though we may say we can’t cure your cancer, the goal is as of right now is to turn this into a chronic disease such as any other chronic disease. Something that you can live with, while managing control. Hopefully, you will continue to enjoy your life and your life won’t be cut short by this cancer.

Katherine:                  

Dr. Phillips, thanks so much for joining us today. We really appreciate it.

Dr. Phillips:                 

No, thank you. I really enjoyed it.

Katherine:                  

And thank you to all of our partners. Please continue to send in your questions to question@powerfulpatients.org. and we’ll work to get them answered in future programs. If you would like to watch this webinar again, there will be a replay available soon. You’ll received an email when it’s ready.

And don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs. To learn more about follicular lymphoma, and to access tools to help you become a more proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today.

What Do You Need to Know About Diffuse Large B-Cell Lymphoma (DLBCL)?

What Do You Need to Know about Diffuse Large B-Cell Lymphoma (DLBCL)? from Patient Empowerment Network on Vimeo.

 After a diffuse large B-cell Lymphoma (DLBCL) diagnosis, what’s important for patients and their loved ones to know? This animated video provides an understanding of DLBCL, available treatment options and lists key steps for becoming an empowered patient.

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Essential Testing Following a DLBCL Diagnosis 


Transcript:

Hi, my name is Dr. Williams, and I am a hematologist-oncologist specializing in diffuse large B-cell lymphoma—commonly known as DLBCL.

Today, I’m going to talk about what you need to know if you or a loved one has been diagnosed with DLBCL.

First, it’s important to understand your disease.

DLBCL is the most common form of non-Hodgkin lymphoma, which is a type of cancer that begins in the lymphatic system. The lymphatic system is part of the body’s immune system and includes tissue and organs that create, carry, and store white blood cells. DLBCL is caused when white blood cells called lymphocytes rapidly grow out of control.

It may be localized to the lymph nodes or may occur OUTSIDE of the lymphatic system in areas such as the thyroid, skin, breast, bone, testes, gastrointestinal tract—or even other organs in the body.

In many cases, an early sign of the disease is swollen lymph nodes. Patients may also experience symptoms that can include fever, unintended weight loss, night sweats, and fatigue. These are known as “B” symptoms. Depending on where the lymphoma is in the body, it could cause other symptoms as well.

Next, it’s important to understand how DLBCL is typically treated.

Because it is fast-growing, treatment usually begins quickly to help control the disease and its symptoms. The standard of treatment is a regimen called R-CHOP, which combines chemotherapy and a monoclonal antibody. This approach can lead to disease remission in many patients.

If a patient doesn’t respond to initial chemotherapy treatment or relapses, then several other types of treatment are considered, such as:

  • Alternative chemotherapy
  • Stem cell transplant
  • Targeted treatment
  • CAR T-cell therapy
  • And clinical trials

When making treatment decisions, factors such as where the disease is in your body, and lab test results can impact available options. And potential side effects, a patient’s age, health, and lifestyle are also taken into consideration.

In addition to understanding your disease and treatment options, it’s vital to be an active partner in your care. So, how can you take steps to be an empowered patient?

  • Educate yourself about DLBCL.
  • Consider a second opinion or consult with a DLBCL specialist immediately following a diagnosis.
  • Write down your questions before and during your appointments. Visit powerfulpatients.org/dlbcl to access office visit planners to help you organize your notes.
  • Understand the goals of treatment and ask whether a clinical trial might be right for you.
  • Bring a friend or loved one to your appointments to help you recall information and to keep track of important details.
  • Finally, remember that you have a voice in your care decisions. Don’t hesitate to ask questions and to share your concerns. You are your own best advocate.

MPN Research and Optimism About Curative Therapies

MPN Research and Optimism About Curative Therapies from Patient Empowerment Network on Vimeo.

Myeloproliferative neoplasm (MPN) researcher Dr. John Mascarenhas discusses why he’s excited about the future of care for patients with essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF).

Dr. John Mascarenhas is Associate Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai. Learn more about Dr. Mascarenhas, here.

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Transcript

Katherine Banwell:

Before we close, Dr. Mascarenhas, let’s talk about research. Are there new developments that you’re excited about?

Dr. Mascarenhas:       

Absolutely. So, what I’m heavily interested in and involved in is clinical investigation and moving the field forward, and there are many people out there that are similarly involved and they’re doing really excellent work. So, I am super jazzed and enthusiastic and optimistic, and it’s what gets me work every day and inspires me is all of the effort that is happening. And, it’s a continuum. So, it’s not just one person trying to try a different drug here and there. It’s really a bringing together of many different people because these are rare diseases.

Many different people from many different institutions that have different areas of expertise, but have a common goal of translating from laboratory informed data, so, not just taking a dart and throwing it at the dartboard and hoping it sticks. But actually taking data that we learned from the lab and leveraging that information to develop therapies that are informed, that are targeted, that are personalized and going through a process of evaluating them to get them into the clinic, with the goal of, and I would say ambitiously, our goal these days is moving beyond trying to make patients feel better, which is an important goal, but it’s really can we really target the disease in a more effective way to induce remissions, to, dare I say, cure patients. So, I think the ambitious goal of the clinical investigators and laboratory investigators that are active in MPN research today is really one looking for an understanding at the basis of the biology of the  disease to develop curative therapies. And, I am optimistic that that will happen.

And, I don’t mean happen in a hundred years from now. I mean happen in our lifetime. So, that’s where we’re going. There’s a lot of very exciting drugs, oral and intravenous drugs and they target very different types of aspects of the disease, and I think patients and physicians will see that maybe those drugs are used best in combination. So, the idea of using one drug, waiting for it to fail and using another drug is really old news, and much of oncology is combination therapy. So, taking drugs that have different targets or mechanisms of action and non-overlapping toxicity to try to better target and delete what’s called the myelofibrosis stem cell that’s the basic issue here, which we don’t effectively delete other than transplant. So, our goal would be to put bone marrow transplanters out of business.

 

An Expert Reflects on Hopeful Advances in Myeloma Treatment

An Expert Reflects on Hopeful Advances in Myeloma Treatment from Patient Empowerment Network on Vimeo.

Research is advancing quickly in myeloma. Donna Catamero, a nurse practitioner specializing in myeloma, shares why she is optimistic about the future of myeloma care and treatment.

Donna Catamero is Associate Director of Myeloma Translational Research at Icahn School of Medicine at Mount Sinai Hospital in New York City.

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Transcript:

Katherine:

When it comes to myeloma research and emerging treatment options, what are you excited about specifically?

Donna:

So, I’m very excited about CAR T therapies, bispecific therapies and even trispecific therapies. And this is really harvesting a patient’s immune system to attack the myeloma cell. And I’m really excited about the results we’re seeing in the clinical trials. We’re seeing for a single agent therapy – and most patients know that with myeloma therapies they’re on combination therapies, but what we’re seeing is, with a single drug, that we can achieve very, very deep responses and very durable remission. So, patients who’ve had several relapses and are on their eighth, ninth, 10th line of therapy – we’re now able to achieve deep and durable remissions, which even five years ago was almost unheard of. So, this is really a very exciting time in myeloma research. 

DLBCL Treatment Decisions: What’s Right for You?

DLBCL Treatment Decisions: What’s Right for You? from Patient Empowerment Network on Vimeo.

When considering therapy for diffuse large b-cell lymphoma (DLBCL), what determines the best treatment for YOU? Lymphoma expert Dr. Loretta Nastoupil shares key decision-making factors, emerging research, and tools for partnering with your healthcare team.

Dr. Loretta Nastoupil is the Director of the Lymphoma Outcomes Database and Section Chief of New Drug Development in the Department of Lymphoma/Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Nastoupil here.

Download Program Guide

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Transcript:

Katherine:

All right. Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re going to discuss how you can be proactive in your DLBCL care and work with your healthcare team to find the best treatment path for you.

Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access information to follow along during this webinar.

At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars.

Finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please, refer to your healthcare team about what might be best for you.

All right. Let’s find out who we’re talking to today. Joining me is Dr. Loretta Nastoupil. Thank you so much for coming on the show with us. Would you please introduce yourself?

Dr. Nastoupil:

Sure. Thanks, Katherine. I’m Loretta Nastoupil. I’m in the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center. I’ve been here since 2013, and I currently lead our new drug development team in our lymphoma section.

Katherine:

Thank you so much for taking time out of your busy schedule to join us. So, let’s start with a basic question, what is diffuse large B-cell lymphoma or DLBCL?

Dr. Nastoupil:

That’s a really important question. And I spend a lot of time when I first meet patients explaining to them there are a lot of different terms that are thrown around in lymphoma. Particularly, non-Hodgkin lymphoma is a term many patients will hear and even use. And I remind them that that is sort of an umbrella term that describes essentially every lymphoma that’s not Hodgkin lymphoma.

So, it’s really important to recognize that there are unique types of large cell lymphoma. And almost everything that we care about in terms of what the treatment will look like, whether or not we’re aiming to cure someone, or just maintain adequate disease control is primarily focused on the type of lymphoma someone has.

So, diffuse large B-cell lymphoma is the most common lymphoma subtype. Just in terms of its descriptive name, it is a B-cell cancer. And it is comprised of large cells that are essentially effacing or replacing the architecture of a lymph node.

There are different types, which I’m sure we’ll discuss. But, again, diffuse large B-cell lymphoma is our most frequent lymphoma we encounter.

Katherine:

What is B cell? What does that mean?

Dr. Nastoupil:

Sure. So, stepping back a little bit, I think most people when they know or have known someone with cancer, it is described as the organ it originates in. So, breast cancer’s a great example. That usually is breast tissue that is abnormal. It has malignant potential. And if it spreads beyond its capsule and specifically goes to a lymph node or another organ, generally that’s bad news.

Lymphoma is a cancer of the immune system. And there are various types of immune cells. B cells – they mature on and become plasma cells when they’re behaving normally. And their job is to generate antibodies so that we can develop immunity from exposures or infections we’ve had and we’ve recovered from.

So, if you develop a cancer in the B cell, depending what stage of development – if it’s a stem cell, for instance, that can lead to acute leukemia. If it’s an immature B cell, meaning it has not developed into a plasma cell, that’s, generally, where diffuse large B-cell lymphoma arises. So, these cells tend to live or spend most of their time in lymph nodes because they’re trying to mimic the behavior of a normal B cell where they’re waiting there for that exposure to happen.

So, these are generally not cancers that we try to cut out before they spread. They’re not spreading cancers in terms of how we generally think of those, meaning you’re not going to use surgery to treat it. And, oftentimes, there are malignant B cells kind of dispersed throughout the body because if you think about how your immune system should work, it should be able to fight off an infection anywhere and everywhere.

So, I think those are key things to keep in mind because oftentimes patients will have widespread involvement or lymph node involvement or bone involvement, and that’s just the nature of the disease and not necessarily something that is so far progressed we didn’t catch it early enough.

Katherine:

I see. Are there subtypes of DLBCL?

Dr. Nastoupil:

Yes, absolutely. So, again, stepping back, over the last 20 years, we have tried to understand why we’re able to cure about 60 percent of patients. But for the 40 percent that were not cured with standard treatment, their outcomes were generally poor, meaning most of those patients died as a result of their lymphoma.

And we’ve approached all of them the same. So, that would imply to us that there’s something inherently different about the large cell lymphoma cases that don’t respond to standard treatment. So, an attempt to try and define who those patients are before we initiate treatment, as technology has evolved, we’ve interrogated some of those biopsy samples to try and understand is there an underlying biologic rationale as to why some patients would have very, very disparate outcomes?

So, what we’ve learned is there are genes that are differentiated between different subtypes of large cell lymphoma. And we’ve described those subtypes based off those gene expression patterns. So, there is a germinal center type of large cell lymphoma. There’s a non-germinal center or activated B-cell type.

And then it gets much more complicated meaning there’s probably far more than just two subtypes. Right now, we’re describing at least five different subtypes. I think what’s important for patients to know is that we view this in terms of being able to predict who’s not going to have the typical course. And if we can define who they are, we might pursue something different, including potentially a clinical trial.

So, the subtypes I care the most about right now in terms of defining are the double hit or double expressors, those with other features that might lend itself to targeted therapy.

So, this is an evolving field and will continue I’m sure – that will have more subtypes defined over time.

Katherine:

Let’s look into testing for a moment. What tests are essential when making a diagnosis?

Dr. Nastoupil:

So, at the beginning, we clearly have to have tissue. I always say, “Tissue is the issue.” So, we may have features that are suggestive of lymphoma. And even sometimes radiologists will describe a CT scan or an x-ray and say, “This looks very suspicious for lymphoma.” But unless we actually have a biopsy that confirms lymphoma, we won’t go as far as to render a diagnosis in the absence of a biopsy.

Now our biopsy approaches have evolved over the last few years. The gold standard or what I would consider to be the best approach currently is to actually have an incisional biopsy meaning we find a lymph node that looks suspicious.

And we either remove the entire lymph node or a large section of that lymph node to render a diagnosis because there’s various things we need to do to that lymph node.

So, generally, we do what’s called immunohistochemistry staining. So, we stain either surface markers of those cells or markers within the cell because cancer is defined as having an abnormal clone or a population of cells that all have the same features. And they’re able to survive even if the host is not thriving.

So, that’s, essentially, what we’re trying to define. Are there cells in this lymph node that are all the same? And what features do they share in common? And then we will also do something called flow cytometry where we’ll take these cells and essentially sort them according to those surface markers. And that will also tell us – is this a B-cell clone, a T-cell clone, and what features would distinguish one lymphoma from another?

And the last thing that we need tissue for are what we call molecular studies, where we may learn about either genes that are rearranged or mutated within those cells that, again, may help us further classify the lymphoma and, again, group them into higher or potentially lower risk groups.

Katherine:

What do the results of these tests tell us about prognosis and treatment choices?

Dr. Nastoupil:

So, again, everything kind of hinges on what type of lymphoma we’re facing. So, for instance, diffuse large B-cell lymphoma is what we call an aggressive lymphoma. So, what does that mean? It can grow very quickly. It can take over the patient in terms of resources. So, generally, patients will have weight loss and sometimes even constitutional symptoms or B symptoms, such as night sweats and fevers, fatigue.

In the absence of treatment, it is universally fatal. Now, that timeline can vary from one person to another. But, generally, within a year, if we don’t treat large cell lymphoma, generally, that’s not survivable.

But as I’ve also mentioned for at least 60 percent of patients and potentially even more, we can cure it with standard treatment. There are other types of lymphoma, such as indolent B-cell lymphomas where actually the goal is not cure, but patients may actually have a normal life expectancy meaning they will face multiple treatment courses over their lifetime. But at the end of the day, they should live just as long as someone their same age and sex who doesn’t have lymphoma.

So, again, that’s gonna be a vastly different treatment course and outcome. So, sometimes, when you’re sitting in the waiting room and you’re sharing your journey with others, you have to keep in mind that you may all be using the same term, non-Hodgkin lymphoma. But our expectations in terms of to and outcomes might be vastly different.

Katherine:

From person to person. What are the stages of DLBCL?

Dr. Nastoupil:

So, we currently use what’s called the Ann Arbor staging system. And, again, this is very different from the staging applied in solid tumors.

And so, the way we define stage is based off where the tumor is in relationship to the diaphragm. So, if you have the disease just in lymph nodes and it’s all confined to one side of the diaphragm, it’s either gonna be stage one or two. And how we distinguish between one or two is just really not are they in close proximity and something that we would fit in one radiation field.

If you have disease that’s above and below the diaphragm, that’s generally at least Stage 3. Stage 4 is generally when it’s now outside of the lymph node. So, what we call extranodal location. So, those are generally organs, lung, liver, skin, bone, etcetera.

It can be very complicated in that you could have just one extranodal site. So, say you just have stomach involvement, or you just have one area of the bone. That could be a 1E.

So, it’s important to recognize every patient has a stage. What that means is whether or not we would give a full course of therapy in terms of systemic treatment that goes through the vein or maybe a shortened course in radiation is dependent on that stage.

Katherine:

Now that we understand a bit more about DLBCL and how it’s staged, let’s move on to treatment options. Many factors come in to play when making a treatment decision, including a patient’s age and overall health. So, let’s walk through some of these considerations. Let’s start with treatment goals. What does this mean exactly? And what are the goals of treatment for DLBCL?

Dr. Nastoupil:

Great questions. For diffuse large B-cell lymphoma, my goal was that I want to eradicate this disease with one course of therapy. Now one course of therapy, again, may mean six cycles of treatment, or it may mean three to four plus/minus radiation. And that kind of gets back to the discussion we just had with stage. But the goal is to make it go away and never come back. Now, oncologists are eternal optimists.

And I saw this because we would not be oncologists if we weren’t always focused and hoping for the best outcomes for our patients.

Katherine:

Sure.

Dr. Nastoupil:

So, we, generally, when we’re counseling patients tend to keep the focus on what is the chance that I can cure this, and we use words like cure oftentimes. But there’s always those caveats. And those caveats are – we can’t really look into our crystal ball and predict the future for every given patient. So, we use tools to help us risk stratify patients, meaning if we took 100 people like a given person, we could predict the outcome for the majority of those patients.

So, with diffuse large B-cell lymphoma with no high-risk features – so, that gets back to the molecular subtype. Do they have double hit features – yes or no? The stage and something we call IPI, International Prognostic Index, that takes into account some clinical features. As you mentioned, patient specific factors, their age, their stage, some lab values, whether or not they have more than one extranodal variable. Then we can generally predict.

Again, if I have 100 patients with good risk IPI, 80 percent of them are likely to be cured and alive and well five to 10 years later. If I have someone with poor risk features that may not change exactly what I do for that patient, but that may help them and me in terms of should I be pursuing a trial to potentially have access to something that’s better than this standard option? Or how does this impact their planning?

Some people are close to retirement. Some people have specific life goals, such as a wedding or an anniversary that sometimes we use those sorts of calculators to best predict the future to inform some of that treatment. So, those are what we call sort of the characteristics coming into treatment.

There are comorbidities or sort of concomitant medical problems, such as heart disease, sometimes diabetes. But, generally, more often than not, it’s how healthy your heart is because my objective with treatment is to cure this.

Cure generally results from chemotherapy. And we can spend some time talking about why have we not moved away from chemotherapy in this disease? But, generally, that does involve chemo because that’s generally how I can eradicate this tumor.

But there are certain situations where that chemo may not be beneficial to a given a patient. It usually has to do with how healthy their heart function is at baseline. So, again, we look at all of these factors. What is their risk with the disease? What is their risk from the toxicity of treatment? And am I able to achieve that goal, which is to eradicate the disease?

Katherine: Well, let’s talk about chemotherapy. Why is that still part of the regimen in a treatment plan?

Dr. Nastoupil:

Yes, I’m gonna borrow an analogy that one of my colleagues Jason Westin uses all the time. The CHOP chemotherapy that is the backbone of our treatment for diffuse large B-cell lymphoma was developed in 1976.

There is no other technology that we would commonly use in our day to day. You wouldn’t still be driving your car you had in 1976. Clearly, our methods of communication in regards to phones have changed dramatically. So, why are we still using chemotherapy that was developed in 1976?

Katherine:

True.

Dr. Nastoupil:

Well, it’s not for lack of trying. Over the last four or five decades, we have been trying to improve upon this. And it works. It works for at least 60 percent of patients. When we tack on targeted therapy, such as immune therapy where we use an antibody that will stick to the surface of a marker on that lymphoma cell and then use the immune system to do some of the heavy lifting, we can probably improve those cure rates from 60 percent to potentially as high as 80 percent. That’s really been the only substantial improvement we’ve made.

Now, there is one caveat. So, just recently, we heard a press release of the POLARIX study, which is the first trial in the last four decades that could potentially replace R-CHOP as the standard of care.

We don’t have the full results yet. It’s essentially utilizing a drug called polatuzumab, which is an antibody drug conjugate. It’s essentially chemo on a stick. But we’re delivering chemo specifically to (CD)79b, which is a target on B cell lymphomas and modifying the CHOPs. We’re not getting rid of chemo altogether. We’re dropping one of the chemotherapy agents and replacing it with this targeted agent. So, it’s essentially CHP plus rituximab and polatuzumab might be the new standard.

But, again, that’s based off many, many efforts to try and replace CHOP. And we’re making slow incremental improvements, but we’re still keeping the therapies that tend to work.

Katherine:

And that makes sense. What about biomarker testing results?

Dr. Nastoupil:

So, in a perfect world, we would be able to take a patient’s specific tumor, sequence it, and provide a recipe or a solution to solve the problem. And that’s what a biomarker is.

It’s something that’s unique to the patient’s given tumor that then would inform what is the best treatment. So, we’re lacking in some ways a perfect scenario. What we do have, as what I’ve mentioned, some molecular studies where we can look for specific genes or rearrangements in the genes that may help us predict the future.

And in diffuse large B-cell lymphoma, one of the most common examples of this is what we call double hit where we’re looking for two genes – MYC, which is M-Y-C, and either BCL2 or BCL6. These are genes that we all have. It’s just the lymphoma has moved these genes into sort of more of a prime real estate location that makes it a little bit more resistant to standard treatments.

So, if you move those genes in that tumor DNA, we call that our rearrangement. And we pick that up based off a FISH study. And if both of those features or all three of those features are there, we call it a double or triple hit.

That’s a potential biomarker that may suggest that particularly R-CHOP or standard treatment may not be the best strategy. There’s some limitations to that conclusion in that that’s not true for every patient. For about 20 percent to 30 percent of patients with double hit features, they’re gonna do really well with R-CHOP.

So, that’s why we are lacking in how effective these biomarkers are. And it would be great if we had additional biomarkers that were more precise or could tell us more than just that the standard may not be optimal.

So, that’s where we’re spending a great deal of time and effort in our research efforts just trying to identify biomarkers that may tell us what’s the best approach for a given patient or what we like to call personalized medicine.

Katherine:

Exactly. Does treatment typically start right away?

Dr. Nastoupil:

Hopefully. So, what I mean by that is everyone has to have a diagnosis. And a common story that I hear is that patients generally know when they’re not doing well. They may not be able to pinpoint I have lymphoma.

But they usually will see a primary care doctor or depending on the location of a lymph node if it’s palpable. Oftentimes, men when they’re shaving will pick up a lymph node in the neck. Or women if they’re having a mammogram will pick up a lymph node in the axillae or under the arm. So, that may lead to further investigation based off the location of a lymph node.

Or it may just be those constitutional symptoms where people aren’t feeling well, and a primary care doctor is their first stop. Lymphoma is rare. So, usually it’s a diagnosis of exclusion or something that we eventually get around to. That is important, but it’s not that important.

So, what I mean by that is I hope patients don’t have any guilt or regret if they’ve been sitting on symptoms for a while or even if their primary care doctor missed signs and symptoms of lymphoma because, again, it’s not very specific. There are a lot of things that can cause similar presentations.

But once we have imaging that is suggestive of lymphoma and then we have a diagnosis that’s rendered, again, followed by a biopsy, generally, then it is important that they seek care.

And they get that care in a timely fashion. What’s kind of interesting is the longer time from diagnosis to the initiation of treatment in diffuse large B-cell lymphoma is usually associated with a better prognosis. So, that’s sort of counterintuitive.

One would think that the sooner you get started on treatment, the better your outcome will be. I think the challenge with interpreting that data is that the longer time from diagnosis to initiation of treatment usually means that that patient’s disease is one that lends itself to the affordability of time to be seen by specialists, have all of your staging studies completed, have a return visit to go over all those results and have a shared decision-making process in terms of deciding what’s the best treatment for you, and then getting started on that treatment.

So, those patients where that is agreeable and acceptable, they’re probably gonna do very well.

For the patients who are really sick and they need to get started on treatment sooner rather later as a result of their disease putting them at risk, either as a result of organs not functioning well or substantial symptom burden as a result of their disease, then they need to get started. So, that’s usually why their course from diagnosis to treatment is generally shorter.

So, again, it all kind of depends on a given situation. But with diffuse large B-cell lymphoma, I tell patients usually within three months of knowing you have lymphoma, we need to get you on treatment, or you’re gonna be sick.

Katherine:

I can imagine. You touched on this a few moments ago. But what do you feel is the patient’s role in this whole decision?

Dr. Nastoupil:

So, I’ve actually been a patient myself, and I have mixed feelings about it. I think oftentimes as an oncologist, we share decision-making when we don’t know the exact path forward, meaning if there’s something controversial or you have more than one option, generally, we kind of put out all the information to the patient, and we want you to be part of that decision-making.

And I think that’s important because we’re all humans, and we all want liberties. And we want our patient rights to be acknowledged and respected. And that’s important. I think sometimes though that also burdens patients with making decisions when they may feel they don’t have all of the information to make an informed decision.

But your role as the patient is you know your body better than anyone. And, generally, if there’s something that just doesn’t fit well or sit well with you, be vocal about it. So, I’ve been in a situation where I felt like I had to speak up a few times, and not that I have all the answers. And I am an oncologist. So, I generally have more insight than others.

But, generally, I was right in that, again, I think we know our own bodies. And when you feel that something is being missed or maybe not given the time and attention it deserves, speak up. You also have a role in making sure that the diagnosis is correct.

So, I generally advise all patients because everything hinges on the diagnosis in lymphoma, more so than the staging, more so than sometimes even the treatment itself.

Getting a second opinion can be incredibly valuable because you have another pathologist that will lay eyes on this biopsy. And lymphoma is rare. So, a second opinion can be incredibly valuable, and that’s usually something driven by a patient more so than an oncologist. Though some oncologists – and I would say the majority – are open to an opinion because they too would like information or confirmation that they’re on the right path.

Katherine:

Certainly.

Dr. Nastoupil:

The other thing that I think patients can have role is exploring what trial options are out there and available to them. I think that is sometimes a tough subject to discuss. Clinical trials are not only for patients who have failed all the standard treatments.

And it’s usually not an option of hospice versus a clinical trial. That’s absolutely an inappropriate time to consider a clinical trial. And, generally, there are trials at any point in a patient’s journey where there is some controversy as to the best path forward.

Again, I’ve been discussing the last 40 years of trying to improve upon R-CHOP is because 60 percent of patients were cured, but 40 percent were not. There is always a scenario where we could do better. And, generally, the only way we will improve upon outcomes is to conduct important rational clinical trials.

So, sometimes, it’s as simple as reaching out, participating in programs such as this, reaching out to the Lymphoma & Leukemia society or the Lymphoma Research Foundation to just explore what are your trial options. They may not be appropriate for you right now but at least understanding where there is an opportunity to participate in a trial is worth exploring.

Dr. Nastoupil:

Dr. Nastoupil, now that we’ve discussed factors that go into the treatment choices, can you walk us through the currently available DLBCL treatment approaches and who they might be right for?

Dr. Nastoupil:

Absolutely. So, again, this is changing, and that’s good news. So, up until recently, R-CHOP or rituximab in combination with CHOP, which is an acronym for four different drugs, cyclophosphamide, doxorubicin, vincristine, and prednisone, has been our standard.

Again, what would potentially challenge that is the POLARIX study where we exchange vincristine for polatuzumab. We don’t know the results of that study yet. All we know is that it met its primary endpoint, meaning it met what it set out to do in terms of improving upon some of the outcomes achieved with R-CHOP.

We need to see the details to know if that means now every newly diagnosed diffuse large B-cell lymphoma patient will be offered the polatuzumab in combination with R-CHP study or whether or not there will still be some patients appropriate for R-CHOP.

But that is generally our first approach. Whether you get six cycles or a shortened course plus/minus radiation depends on your state. Once patients have completed therapy, generally, then we pursue what’s called surveillance.

So, we’re monitoring for any signs that the lymphoma has recurred or has not gone away. That’s a controversial topic in terms of how to conduct surveillance and one that I suspect will change over time. But for most patients, if the lymphoma is going to recur, it generally recurs within the first two years.

So, assessing patients either in the form of a CT scan, a PET CT, or a physical exam with labs every four to six months for the first two years is what most practices will pursue. I’m not saying that there is no chance that you would relapse beyond two years. It’s just that the majority of patients, at least 90 percent, if the lymphoma comes back, it usually does so within two years.

And the relapses that occur beyond two years are less predictable. They could happen at three years. They could happen at 10 years, as it’s hard to know how to do surveillance beyond two years.

If the lymphoma recurs, the first thing we need to do is biopsy it because there are many things that can mimic lymphoma on a scan – infection, inflammation, other tumor types. So, if there is ever a question about whether or not the lymphoma has recurred, I generally advise for all patients they undergo a biopsy to ensure that we know what we’re treating.

Depending on when the lymphoma recurs, if it happens within 12 months, this is another area that we are shifting our practice. In the past, for all patients who had relapsed large cell lymphoma, we would pursue what we call salvage or second-line chemotherapy. So, we mix up the chemo. We keep, generally, the rituximab, but we alter the chemotherapy agents. We wouldn’t give CHOP again.

And then we give a shortened course where we give two to three cycles. We repeat the scan. And for patients who’ve achieved what we call chemo-sensitive disease – so, that’s generally a complete response on scan – we would then move forward with high-dose therapy and an autologous stem cell transplant. So, essentially giving different but more intense chemo and rescuing patients from that maneuver with their own stem cells that will go back to the bone marrow and start making white blood cells, red cells, and platelets again.

What has shifted in the last six months is we now know that CAR T-cell therapy is superior to that approach, at least with two CAR Ts for patients whose lymphoma came back within 12 months. Again, we’re eagerly awaiting the full results of those randomized studies. But three trials were conducted. Two of the three suggest CAR T is better than second chemo and transplant for those patients who relapse within 12 months.

So, currently, we think that you’ll have a CHOP-like therapy with plus rituximab frontline. If you progress within 12 months, you potentially would be a candidate for CAR T-cell therapy. If the CAR T-cell therapy fails, which is true for about half of patients, or if you’re deemed to not be a candidate for CAR T, we have several other new options that didn’t exist a year ago, including targeted or non-chemotherapy options.

So, there are at least four options in that setting now that are therapies that target the lymphoma cells, either by targeting CD19, which is another surface marker, augmenting that either with an antibody drug conjugate, such as Lonca, or with an immune therapy, such as lenalidomide and tafasitamab. Polatuzumab is available in that third line or later space combined with bendamustine and rituximab. There’s an oral agent called Selinexor.

So, a lot of that is not to burden patients with information but to let them know they’ve got lots of options. And many of these can be sequenced. So, if we can’t achieve cure with R-CHOP and/or CAR T, there are still very good outcomes in that third line or later space.

Katherine:

We’ve covered a lot of information here so far. And just a reminder that the resource guide I mentioned earlier contains definitions and resources for what we’re discussing today. So, be sure to click on that link if you haven’t already.

Dr. Nastoupil, I’m wondering how patients can feel confident in speaking up and becoming a partner in their care.

Dr. Nastoupil:

So, it’s important to recognize, and I reflect on this all the time. Generally, once patients have been rendered a diagnosis of cancer, that’s a life-altering event. And even if I spend a lot of time trying to reassure patients that outcomes for lymphoma patients are very good, generally we’re aiming for cure, that’s not true for everyone.

And you can’t help but be concerned that you will succumb to this disease or that the toxicity of therapy is gonna be life-altering and impact your quality of life in such a way that it’s no longer the life that you were happy to live.

And so, I recognize that we are partners in this. My job is to choose the most effective therapy that will try and accomplish the goals we set out to achieve. However, sometimes, oncologists make assumptions about what the goal of a given patient is.

We’re assuming that longevity or living is the most important goal. Whereas sometimes, people might care more about the quality of life, or they may need more reassurances about what the options are or their realistic outcomes with therapy. Because, again, I’ve mentioned before, oncologists are generally eternal optimists. We tend to sugarcoat things a little bit.
So, it’s important for patients to recognize that they will have a shared decision responsibility, meaning oftentimes we will provide all the information that we have access to in terms of a given treatment.
What is the likelihood of success, what is the potential risk in terms of toxicity, and what we’re leaning towards one therapy over another, particularly if you have more than one option.
But, ultimately, we need patients to share with us what their goals are in terms of outcome of that treatment so that we can then potentially refine our treatment selection. So, again, being informed, participating in programs like this so that you understand what makes one lymphoma different from another. Why would one oncologist offer one treatment and another discuss something else?

So, understanding what the different lymphomas are, how they might be approached differently, what the new therapies are. I struggle to keep up with just the lymphoma literature and changes. I can’t imagine what it must be like for an oncologist that treats every cancer type. So, again, understanding that new drugs are approved almost every couple of months in lymphoma may provide an opportunity for patients to share new information with their oncologists as well. So, information is key.

Katherine:

Dr. Nastoupil, thank you so much for taking the time to join us today.

Dr. Nastoupil:

Well, I appreciate your time as well.

Katherine:

And thank you to all of our partners.

If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs.
To learn more about DLBCL and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us today.

Myeloma Treatment: When Should a Clinical Trial Be Considered?

Myeloma Treatment: When Should a Clinical Trial Be Considered? from Patient Empowerment Network on Vimeo.

 At what point should a clinical trial be an option for myeloma treatment? Dr. Joshua Richter shares his perspective on the appropriate time to weigh clinical trial participation and the potential benefits.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

See More From Engage Myeloma


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Transcript:

Katherine:

When should a clinical trial be considered for myeloma treatment?

Dr. Richter:

So, clinical trials are an extremely important component of how we manage myeloma. And I think there are a lot of myths and misconceptions about trials. Trials are not always things to do after everything else failed. From my standpoint, at every point along the way, we should always consider clinical trials, because they offer something really amazing. They offer us access to drugs way before they’re approved.

And the benefit of not waiting until the end, after you’ve been through everything else, is two-fold. One, in order to get on a trial, you need to fit certain criteria, inclusion, and exclusion criteria. You need to have myeloma, but you can’t be so sick from other medical problems that you’re not going to tolerate that treatment well. As such, unfortunately, some patients after they’ve been through all the other therapies may not qualify for a clinical trial, and that can be really upsetting.

The other benefit of doing a clinical trial early on is if you go on a new drug and it doesn’t work, you have all of the other standard of care options available at a moment’s notice. But if it does work and you gain access to a drug way before it’s approved, and it happens to work extremely well in you, you can have an unbelievably long remission and still have all of the drugs that are available. And, potentially, in that time on the drug, new standard of care drugs are approved. It even deepens the well that you can reach into to grab more options. So, at all times along the way, it’s always important to weigh the risks and benefits of what we call standard of care treatment versus clinical trial options.

Staying Updated on AML Research News: Advice From an Expert

Staying Updated on AML Research News: Advice from an Expert from Patient Empowerment Network on Vimeo.

Dr. Jeffrey Lancet, an AML expert from Moffitt Cancer Center, shares tips for sifting through research news and encourages communication with your healthcare team about what you’ve learned.

Dr. Jeffrey Lancet is Chair and Program Lead in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. He is nationally and internationally recognized for his clinical research in the field of acute leukemias. Learn more about Dr. Lancet, here.

Download Program Resource Guide

See More From INSIST! AML

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Transcript:

Katherine:      

Well, patients are often educating themselves about developing research and new treatment options. Do you have advice for patients who, when it comes to talking with their doctors about what they’ve learned?

Dr. Lancet:                   

I think it’s important for patients to speak to their doctors directly and as soon as possible as opposed to going on the internet and doing a Google search for this drug or that because every patient’s situation is unique and how to apply these new drugs is very different amongst patients.

And some patients may qualify for certain approaches and others do not. So, it’s very important to talk to your doctor about how you can individualize your treatment based upon your specific scenario. What type of mutation does a patient have, what is their level of fitness, are they potentially candidates for bone marrow transplant? Those are some of the basic questions that come up all the time to determine what is the best treatment approach.

And as we’re developing new therapies, and more of them, there will be more options for patients and a more personalized approach that can be taken that really can only be decided based upon that individual patient’s unique profile. So, it’s very important to really recognize that one size does not fit all when it comes to treatment of this disease and that certain drugs may be helpful and certain drugs may be unhelpful in that particular site.

Katherine:                   

What would you like to leave patients with today? Are you hopeful about the future of AML treatment and research?

Dr. Lancet:                   

Yes, I’m very hopeful. I think AML is a disease that is really a very diverse and complex one. It doesn’t lend itself well to huge immediate breakthrough therapies that will immediately change the landscape by double digit percentages for example. This is a disease that, again is very complex, and in which advances are made slowly but steadily. And I think we’ve seen that over the past to 5 to 10 years is that we are gradually incorporating new drugs into our treatment regimens with gradually increasing levels of success as we learn more about these drugs starting out as single agents and then beginning to combine them.

I think that we’re learning an awful lot about the molecular landscape about AML and how it impacts treatments and treatment decisions and prognoses. I think our ability now to detect what we recall measurable residual disease is very important. Also, because now we can get a grasp of how well our treatments are working and are we knocking out enough bad cells to expect good outcomes, and if we’re not, then hopefully we can intervene and kind of hit it while it’s down so to speak and use some of these new therapies to knock out what might be left over to give patients better overall long term responses and results.

So, definitely reason to be hopeful, but we have to stay patient as well. It’s difficult because it’s a, it’s a terrible disease but we have to recognize that it’s something that requires very careful research to develop the appropriate clinical trials that will have the highest chance of success.

Katherine:                   

Dr. Lancet, thanks so much for joining us today.

Dr. Lancet:                   

Thank you very much for having me. It was good to be with you and I appreciate the opportunity.

Katherine:

And thank you to our audience. I’m Katherine Banwell.

 

 

 

AML Research Updates: News From ASH 2020

AML Research Updates: News from ASH 2020 from Patient Empowerment Network on Vimeo.

AML expert Dr. Jeffrey Lancet shares the latest news from the 2020 American Society of Hematology (ASH) annual meeting. Dr. Lancet sheds light on headlines from the meeting including FLT3 inhibitor research, combination therapies with venetoclax, a promising inhibitor therapy, and shares his optimism about the future of AML treatment.

Dr. Jeffrey Lancet is Chair and Program Lead in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. He is nationally and internationally recognized for his clinical research in the field of acute leukemias. Learn more about Dr. Lancet, here.

Download Program Resource Guide

See More From INSIST! AML

Related Resources:

Navigating AML Treatment Decisions

New AML Therapies vs. Traditional Chemotherapy: What’s the Difference?

Transcript:

Katherine:      

Hello, and welcome. I’m Katherine Banwell. Today we’ll discuss the latest news from ASH 2020 and how AML patients can advocate for personalized care. Joining me is Dr. Jeffrey Lancet. Welcome. Would you please introduce yourself?

Dr. Lancet:                   

Hi, sure. My name is Dr. Jeff Lancet. I’m at the Moffitt Cancer Center in Tampa, Florida, where I am the Chair of the Malignant Hematology Department. We spend a lot of time treating patients and conducting clinical trials of Acute Myelogenous Leukemia.

Katherine:                   

Okay. Thank you. Dr. Lancet, the American Society of Hematology Annual Meeting just closed. What are the AML headlines from this year’s meeting?

Dr. Lancet:                   

Yeah, so as usual, AML was a very busy area for clinical presentations this year at the ASH meeting focusing largely on novel and targeted therapies.

I don’t believe that there were many practice changing developments per se, but rather discussions about many promising therapeutic strategies that are still under development and moving forward rapidly largely in the areas of targeted therapy, low intensity therapy, measurable residual disease and things of that nature.

Katherine:                   

What does this research news mean for patients?

Dr. Lancet:                   

Well, I think that there’s a lot to be encouraged about and maybe I’ll take the time to review some of the highlights in what was presented with respect to some of the novel therapeutic approaches that many of our patients can look forward to receiving in the not too distant future.

So, we often talk about you know, targeted therapies and, of course, one of the major targets over the years has been that of mutated FLT3 which is one of the most common mutations in AML.

And at this meeting we saw several presentations on clinical trials resolved to utilizing inhibitors of FLT3, with some emphasis on the most recently approved second generation drug called gilteritinib.

There were I thought three major presentations focusing on gilteritinib and one was an update on a randomized Phase III trial comparing gilteritinib plus azacitidine versus azacitidine alone in newly diagnosed unfit for induction chemotherapy patients with FLT3 mutations, preliminarily showing good tolerability and high composite complete response rates in the combination on.

There was another trial of gilteritinib plus venetoclax in relapsed and refractory FLT3 mutated AML.

And what was interesting was that a very high percentage of patients achieved response with this combination of gilteritinib plus venetoclax, many of whom were heavily pretreated previously and many of whom had also gotten prior FLT3 inhibitor therapy during an early stage of the disease. So, the combination of gilteritinib and venetoclax and this more refractive study, it was encouraging to see these promising responses.

And then we saw some data reporting the effects of gilteritinib in combination with more traditional chemotherapy induction with a couple of studies demonstrating both a high complete response rates as well as high rates of mutation clearance of the FLT3 mutation.

So, those were very encouraging data that were presented with respect to the FLT3 mutated AML population.      

So, another very important drug that reached the marketplace for AML recently is a drug called venetoclax, which is an inhibitor of a protein called BCL2.

And this drug was recently FDA approved for use in combination with low intensity chemotherapy drugs such as azacitidine or decitabine.

And it seems as though the combination of venetoclax plus one of these hypomethylating agent drugs, azacitidine or decitabine has resulted in very, very strong efficacy signals as recently published in a New England Journal of Medicine paper that reported on the results of the Phase III trial of venetoclax plus azacitidine.

So, that has now become standard of care for older less fit adults with newly diagnosed AML; the combination of venetoclax plus a hypomethylating agent such as azacitidine.

And naturally, there’s been interest in really kind of taking it several steps further to advance the role of these combinations and to also look at additional drugs in combination with venetoclax plus hypomethylating agent therapy.

So, we saw some of that at the ASH meeting this year. One approach would be to take venetoclax and then to combine it with more intensive chemotherapy for perhaps more fit patients or younger patients that could undergo a more intensive program.

So, we saw presentations of venetoclax being combined with a drug called CPX-351, which is a novel liposome formulation of two common chemotherapy drugs that had been approved a few years ago for secondary AML. And we also saw a combination strategy with venetoclax, and a regimen known as FLAG-IDA, which is a commonly used induction regimen in acute myeloid leukemia.

And I think it’s important to recognize that although these trials that combine the venetoclax with more intensive chemotherapy showed signs of good efficacy with good response rates, there were definitely signals of increased toxicity, hematologic toxicity primarily, which is not completely unexpected with venetoclax knowing that it can cause significant lowering of white blood cells and platelets and hemoglobin.

And then finally, there is a lot of interest in, you know, doing these types of combinations with venetoclax in different subsets of AML and one subset of AML that has been very important recently is that of the IDH mutated AML population of patients.

IDH is a fairly common mutation that occurs either in the Isoform of IDH1 or IDH2 and there’s about a 15 to 20 percent incidence of IDH mutations in AML.

Now we do have an inhibitor for both of these types of mutations: ivosidenib for IDH1 and enasidenib for IDH2, but there also appears to be a strong role for venetoclax plus azacitidine in IDH mutated AML.

We saw from a series of patients presented by a physician at MD Anderson looking at outcomes with venetoclax plus azacitidine in IDH mutated AML. And the response rates were very high when you give HMA plus venetoclax to these patients with IDH mutated AML.

But I think more importantly was that there were what we call high intro patient response rates when switching between venetoclax and HMA therapy with an IDH inhibitor containing regimen.

In other words, a patient would have a good chance of responding to the initial therapy and then if or when that therapy stops working, having a good effect from a salvage therapy with the other regimen. So, when you see initially azacitidine plus venetoclax and then had a relapse, the IDH inhibitors worked well and vice versa if you had received an IDH inhibitor and then subsequently received HMA-venetoclax at a later time point that also worked well.

So, it’s encouraging to see that you can potentially sequence these drugs and get continued responses along the way and ultimately we think will help a survivor and keep patients in a better state of health even longer.               

So, I just wanted to take a few minutes also and discuss some of the newer more novel therapies that are really hitting or approaching the landscape right now. One of these is called CC486, also known as oral azacitidine or ONUREG. And this drug was shown in recent literature to prolong overall survival in patients who are in first remission from their AML who had received induction chemotherapy.

So, this drug was used as maintenance therapy after a variable number of consolidation regimens. And people who got this ONUREG or oral azacitidine drug as maintenance therapy, it resulted in longer survival compared to those who had received placebo.

And this was presented at last year’s ASH meeting, but this year’s ASH meeting provided an update, a very important update, showing that the overall survival advantage from this drug, this oral azacitidine drug, when used as maintenance was independent of whether a patient had measurable residual disease at the time that they went onto the maintenance therapy.

In other words, whether you had MRD, measurable residual disease or not at the time of the study entry, your responses were still more favorable, your outcomes were more favorable, if you received this oral azacitidine drug.

So, this was FDA approved earlier this year for patients in the maintenance phase of therapy for AML who had gotten prior reduction chemotherapy.

And importantly, this drug was also shown to be able to convert about 25% of patients who were positive for measurable residual disease; convert them from positive to negative. So, even though they were in remission, they had measurable residual disease and this drug in about 25 percent of the cases converted that from positive to negative. So, that’s a very important finding as well.

Another important drug that I think you should keep your eye on is a drug called magrolimab. This is an antibody against a certain type of protein that is present on the immune system cell called the macrophage, and when this magrolimab drug was combined with azacitidine in a recent clinical trial, it was demonstrated very high response rates of over 65 percent.

And, in particular, in patients with P53 mutations, which is a very bad mutation to have in most cancers, including AML, in patients with this high-risk mutation, the combination of magrolimab with azacitidine appears to be effective based upon the early data that we have with high response rates.

And then finally, I just wanted to make mention of another important area in, not really just AML, but in all cancer and that’s  outcomes disparities between different races and ethnic groups. And we saw a very important presentation at the plenary session this year where the authors reported outcomes amongst younger patients with AML who were African American compared with Caucasian.

And the data clearly indicated a worse overall survival amongst Black patients compared with white patients under age 60. And this included patients who were enrolled in clinical trials. So, that it appeared that African American patients have a worse outcome than Caucasian patients with acute myeloid leukemia highlighting the need to better understand various risk factors and other factors that play into these disparate outcomes between our Black American population and a white American population, which I think could shed light on additional disease characteristics that may help everybody as well.

 

Advocating for Key AML Testing: Advice From an Expert

Advocating for Key AML Testing: Advice From an Expert from Patient Empowerment Network on Vimeo.

Dr. Hetty Carraway, an AML specialist at Cleveland Clinic, shares advice on advocating for yourself when diagnosed with AML, underscoring the importance of asking questions, and including your caregiver as part of the conversation.

Dr. Hetty Carraway is Director of the Leukemia Program at Cleveland Clinic. Dr. Carraway cares for patients with acute leukemia and bone marrow failure states. Learn more about Dr. Carraway, here.

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 Treatment Approaches in AML: Key Testing for Personalized Care

 New AML Therapies vs. Traditional Chemotherapy: What’s the Difference?

 Understanding Risk in AML: How Molecular Testing Affects Treatment Options

Transcript:

Katherine:

What advice do you have for patients when it comes to asking for appropriate testing and speaking up in their own care?

Dr. Carraway:            

This is so important. I think patients are leery to stir the pot or be difficult. I think coming from a place of inquiry, teach me about this, that, or the other thing, help me understand this, that, or the other thing – I would like you to show me why this decision or talk with me about why this decision versus another decision might be better for me compared to somebody else.

I can’t underscore the importance of advocating for yourself and asking questions about why am I getting this drug? What are the side effects to this drug? What is my prognosis? What is different about my case versus somebody else’s situation? How do I best prepare myself in getting ready for the therapy that I’m about to go through?

Those are all important questions that patients should ask. They should certainly have people, if possible in their family be advocates for them. I welcome that, and I think that that’s a really important part of going through this type of therapy for any patient. Your physician should welcome having your involvement in that. Don’t be shy about that. It’s your health, and any investment in that the most important people in that is inclusive of you and your caregivers. They should be a welcome part of the team.

Understanding AML Induction and Consolidation Therapy

Understanding AML Induction and Consolidation Therapy from Patient Empowerment Network on Vimeo.

Dr. Hetty Carraway, an AML specialist at Cleveland Clinic, provides an explanation of the role of induction and consolidation therapy in AML patients.

Dr. Hetty Carraway is Director of the Leukemia Program at Cleveland Clinic. Dr. Carraway cares for patients with acute leukemia and bone marrow failure states. Learn more about Dr. Carraway, here.

See More From INSIST! AML

Related Resources:


 Treatment Approaches in AML: Key Testing for Personalized Care

 New AML Therapies vs. Traditional Chemotherapy: What’s the Difference?

 Understanding Risk in AML: How Molecular Testing Affects Treatment Options

Transcript:

Katherine:

Would you define induction therapy and consolidation therapy and tell us what the differences are?

Dr. Carraway:            

For most patients that are diagnosed with an acute myeloid leukemia, over the last 30 to 40 years we’ve used an intensive chemotherapy regimen that we call induction. Induction means that we’re trying to get the leukemia into remission with an intensive chemotherapy regimen. Classically, that has been two agents; one, a cytarabine based regimen along with an anthracycline, either idarubicin, danorubicin, or some anthracycline that’s similar.

Now, the cytarabine based therapy is a continuous infusion over seven days. The anthracycline is given over three days as an intravenous IV push, and so that’s why it’s kind of been nicknamed seven and three – seven days of cytarabine and three days of another anthracycline.

Now, that has constituted the induction intensive regimen in the hospital with the idea that that leukemia gets under control and goes away. More recently for patients, they can receive therapy that is not this inpatient, in-hospital, induction chemotherapy but rather use oral therapy combining with venetoclax, which is a Bcl-2 inhibitor, along with azacitidine, which is either IV or subcutaneous given to patients over seven days. The oral, venetoclax is every day.

That type of induction can also be given and is now an outpatient regimen and more often offered to patients that are older, over the age of 75.

That, too can be considered induction with the idea that once a patient is diagnosed with leukemia this regimen is started, and after one month or even two months on venetoclax plus azacitidine patients’ leukemia can get into what we call remission, where the blast percentages are less than 5 percent. Then, normal hematopoiesis of platelets being greater than 100,000 and a neutrophil count greater than 500 or 1,000, and the patient is then transfusion-independent.

In general, induction chemotherapy is that first round of chemotherapy that’s trying to get the leukemia under control.

Consolidation chemotherapy is when you use subsequent cycles of chemotherapy to keep the leukemia under control because we know that if we don’t continue to give some continuation of therapy that the small, little seeds of leukemia will re-emerge and leukemia will relapse.

Navigating AML Treatment Decisions

Navigating AML Treatment Decisions from Patient Empowerment Network on Vimeo.

What factors can help determine the best treatment path for your AML? This animated video walks through important considerations that may help in navigating treatment decisions, including how genetic testing results, treatment goals and patient preference can impact your choice.

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Genetic Mutations That Affect AML Prognosis and Treatment

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Effective AML Combination Treatment

Transcript:

Hi, I’m Gina. I’m a nurse practitioner and I specialize in acute myeloid leukemia, or AML.

When diagnosed with AML, it’s important to take steps to get a deeper understanding of your disease, and the available treatment options, so that you can feel confident in your care decisions.

Before we walk through the important steps to decide on a treatment path, I want to remind you that this video is intended to help educate AML patients and their loved ones and shouldn’t be a replacement for advice from your doctor.

OK, let’s get started.

The first step is to understand your diagnosis, so that you can find out what treatments are available to you. Unlike solid tumor cancers, such as lung or breast cancer, AML is not staged. Instead, your physician will use lab testing, including blood and bone marrow tests, to determine the subtype of your AML and if you have any chromosomal abnormalities to determine if your AML is low, intermediate or high-risk.

Knowing your risk can impact your prognosis and help establish the best treatment option for you. If you don’t know your subtype, ask your doctor for the information and if you may need further testing to reach a more accurate diagnosis.

Testing that identifies characteristics unique to YOUR AML can impact your treatment options and determine if a targeted therapy or immunotherapy might be more effective. These tests include:

  • Molecular testing
  • Cytogenetic analysis (or karyotyping), and
  • Fluorescence in situ hybridization also known as a FISH test

Before you start any treatment, it’s essential to insist that you have had relevant testing.

Next, you should understand treatment goals. The first goal of AML therapy is to get into remission. The second goal is to maintain that remission.

Induction therapy, or the first phase of treatment, is meant to induce remission. This first-line treatment kills as much of the disease as possible and returns blood counts back to normal.

Consolidation treatment, also referred to as post-remission therapy, is used to prevent leukemia cells from returning and maintain remission. In some patients, stem cell transplant acts as a consolidation therapy. In others, additional treatment options to maintain remission can be explored.

The next step is to consider your treatment options with your doctor. It’s important to understand the approaches available for YOUR individual disease. AML treatments can include:

  • Chemotherapy
  • Targeted therapy
  • Stem cell transplant
  • Immunotherapy
  • Clinical trials, which may provide access to treatments that are not yet approved.

Or, you may receive a combination of one or more of these treatments.

Once you understand the therapies that are available to you, it’s time to talk to your doctor about the risks and benefits of each option. Your doctor will also consider your age, overall health, and existing conditions before suggesting a treatment course.

So, what questions should you address when discussing your treatment goals with your doctor? Consider asking:

  • Is stem cell transplant a viable option for you?
  • Can you tolerate high-intensity therapy or is low-intensity therapy better for you?
  • How will the treatment impact your quality of life and lifestyle?
  • Are there short or long-term treatment side effects that may occur after you have completed treatment?
  • What is the plan if the first approach to treatment isn’t effective?
  • Is there a clinical trial that might be right for you?
  • Is there a member of the team, such as a social worker, that can help you understand the potential treatment costs? And is there access to financial resources that can help you if needed?

Remember that you have a role in making decisions regarding your care. Insist that all of your questions are answered when making a decision with your healthcare team. If you don’t feel supported or you don’t feel heard by your healthcare team, then it is always best to seek a second opinion.

Finally, once you have gathered all the information, it may be helpful to talk it out with people you trust, such as a partner, friend or family member, to help you make a decision that you feel confident about.

Now, how can you put this information to work for you?

  • Ensure that you have an accurate understanding of your diagnosis.
  • Make sure you have had appropriate testing to establish your subtype and risk.
  • Understand your treatment options and talk with your doctor about what’s best for YOUR AML.
  • Remember, you are a partner in your care and have an active voice in finding the best treatment for you.

Visit powerfulpatients.org/aml to learn more about AML.